The possibility exists that abnormalities in apolipoprotein metabolism may play an etiological role in one or more of the hyperlipoproteinemias. The present study is concerned with evaluating the turnover kinetics and catabolic site(s) of one of the major apolipoproteins, using a laboratory animal model. Our approach in this study is based on the concept that the plasma lipoprotein system consists of families of lipoproteins (e.g. lipoprotein A, lipoprotein B and lipoprotein C), each of which is characterized by a distinct protein moiety (e.g. apolipoprotein A, apolipoprotein B and apolipoprotein C, respectively) representing unique chemical and biochemial characteristics of each family. Our working hypothesis is that each apolipoprotein is a major determinant of the metabolic characteristics of its lipoprotein family. Our proposal focuses on apolipoprotein A (ApoA) metabolism. Current technology is available for solubilization, purification and I125 labeling of this apolipoprotein. Our studies utilize the dog which is an ideal model because of its high concentrations of ApoA and the lipoprotein A family as major cholesterol carrier in plasma. Extensive preliminary investigations have established basic methodology in our laboratory. After purification, ApoA is iodinated by the McFarlane procedure. I125-ApoA is then administered and periodic blood samples are obtained for measurements of turnover kinetics. Preliminary studies of the catabolic site(s) involved in ApoA metabolism have been undertaken to evaluate the tissue distribution of radioactivity after I125-ApoA administration, as well as its binding to subcellular site(s). Additional studies are outlined to characterize the role of specific cellular componenets in this ApoA catabolism.